Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LUOJin-long ^1,2 ,  JIANGHuai-wu ¹

1. Department of Gastrointestinal Surgery, Sichuan Mianyang 404 Hospital, Mianyang 621000, Sichuan Province, China;
2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan Province, China;

Corresponding author：

JIANGHuai-wu, Email: jhuaiwu@163.com

Keywords：

Placental growth factor; Gastric cancer; Clinical significance

DOI：

10.7507/1007-9424.20150285

Video：

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Objective To investigate the relationship between placental growth factor (PlGF) and the gastric cancer. Methods The cancer tissues (cancer tissue group) and para-cancer tissues (para-cancer tissue group) of 88 patients with gastric cancer who underwent surgery in Sichuan Mianyang 404 Hospital from Mar. 2013 to Dec. 2014 were collected retrospectively, to determine the expressions of PlGF mRNA and its protein by polymerase chain reaction (PCR) and immunohistochemistry method. In addition, blood samples of 30 normal persons (normal person group) who got examina-tion in Sichuan Mianyang 404 Hospital in Sep. 2014 and 88 patients with gastric cancer (gastric cancer group) were collected to detect the concentration of serum PlGF, by using enzyme linked immunosorbent assay (ELISA). Comparison of the expressions of PlGF mRNA and its protein between cancer tissue group and para-cancer tissue group, concentration of PlGF between cancer tissue group and normal person group were performed, as well as the relationship between expressions of serum PlGF mRNA/PlGF in gastric cancer tissues and clinicopathological features of patients with gastric cancer, and relationship between concentration of PlGF in blood and clinicopathological features of patients with gastric cancer was explored by univariate analysis. Results The expression level of PlGF mRNA (0.569±0.166 vs. 0.037±0.020, t=-29.948, P=0.000) and positive-expression rate of PlGF[80.7% (71/88) vs. 5.7% (5/88), χ²=100.867, P=0.000] were significantly higher in cancer tissue group than those of para-cancer tissue group. And the concentration of PlGF in blood of patients in gastric cancer group was higher than that of normal person group[(57.247±9.800) ng/L vs. (10.351±1.715) ng/L, t=43.000, P=0.000]. The expressions of PlGF mRNA and its protein were both correlated with diameter of tumor, pT staging, pN staging, differentiation, and Borrmann type (P<0.050). The expression levels of PlGF mRNA and its protein in that patients with diameter of tumor greater than 4 cm, pT3-4 staging, pN3 staging, low differentiation, and Borrmann Ⅲ-Ⅳ staging were higher. While there were no significant correlation between expressions of PlGF mRNA/protein and age, gender, pM staging, and gastrointestinal type (P>0.050). Concentration of serum PlGF of gastric cancer patient wasn't significantly correlated with age, gender, diameter of tumor, pT staging, pN staging, pM staging, differentiation, Borrmann type, and gastrointestinal type (P>0.050). Conclusion The abnormal expression of PlGF at gastric cancer tissues may play an important role in pathogenesis of gastric cancer.

Citation： LUOJin-long, JIANGHuai-wu. Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(9): 1101-1106. doi: 10.7507/1007-9424.20150285 Copy

1.	陈静, 张德巍, 张春东, 等. 术前血清CEA、CA19-9水平检测对胃癌术后复发转移及预后的意义. 中国普外基础与临床杂志, 2015, 22(2):195-199.
2.	Rasmussen JG, Riis SE, Frøbert O, et al. Activation of protease-activated receptor 2 induces VEGF independently of HIF-1. PLoS One, 2012, 7(9):e46087.
3.	石岩岩, 丁士刚. 胃癌病因及发病机制的研究进展. 中华临床医师杂志:电子版, 2013, 7(17):7941-7944.
4.	Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res, 2002, 62(10):2749-2752.
5.	Chang LH, Pan SL, Lai CY, et al. Activated PAR-2 regulates panc-reatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis. Am J Pathol, 2013, 183(2):566-575.
6.	张示杰, 吴何兴, 李琪, 等. 沙鼠肝泡球蚴组织中微血管密度、血管内皮生长因子的表达及意义. 中国普外基础与临床杂志, 2015, 22(2):134-138.
7.	Parr C, Watkins G, Boulton M, et al. Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur J Cancer, 2005, 41(18):2819-2827.
8.	Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell cancer:an association with clinical characteristics and vascular endothelial growth factor levels. Anticancer Res, 2003, 23(6D):4953-4958.
9.	Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in lung cancer. Tumor Biol, 2004, 25(1-2):1-6.
10.	Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma-2nd English edition. Gastric Cancer, 1998, 1(1):10-24.
11.	罗旭. PLGF、TGF β1和bFGF在膀胱移行细胞癌中的表达及临床意义. 遵义:遵义医学院, 2009:1-30.
12.	沈承澜, 沈振斌, 陈伟东. 血管内皮生长因子、缺氧诱导因子-1α在胃癌中的表达及其对预后影响的研究. 中国全科医学, 2010, 13(22):2460-2463.
13.	De Falco S. The discovery of placenta growth factor and its biolo-gical activity. Exp Mol Med, 2012, 44(1):1-9.
14.	Boyaud F, Inguimbert N. Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475). Expert Opin Ther Pat, 2011, 21(6):971-975.
15.	Xu L, Cochran DM, Tong RT, et al. Placenta growth factor overex-pression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res, 2006, 66(8):3971-3977.
16.	张力建, 陈晋峰, 陆爱萍, 等. 胎盘生长因子和色素上皮衍生因子在非小细胞肺癌中的表达及其与预后的关系. 中华医学杂志, 2005, 85(47):3328-3331.
17.	Waldner MJ, Neurath MF. Colitis-associated cancer:the role of T cells in tumor development. Semin Immunopathol, 2009, 31(2):249-256.
18.	Fitzpatrick TE, Lash GE, Yanaihara A, et al. Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor. Exp Cell Res, 2003, 283(2):247-255.
19.	Lenderink T, Heeschen C, Fichtlscherer S, et al. Elevated placental growth factor levels are associated with adverse outcomes at four-year follow-up in patients with acute coronary syndromes. J Am Coll Cardiol, 2006, 47(2):307-311.
20.	Takahashi A, Sasaki H, Kim SJ, et al. Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. Biochem Biophys Res Commun, 1999, 257(3):855-859.
21.	Ho MC, Chen CN, Lee H, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett, 2007, 250(2):237-249.
22.	Hamady ZZ, Cameron IC, Wyatt J, et al. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis:a critical appraisal of the 1 cm rule. Eur J Surg Oncol, 2006, 32(5):557-563.
23.	Kodama J, Seki N, Tokumo K, et al. Placenta growth factor is abundantly expressed in human cervical squamous cell carcinoma. Eur J Gynaecol Oncol, 1997, 18(6):508-510.
24.	Sands M, Howell K, Costello CM, et al. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res, 2011, 12:17.
25.	Yao J, Wu X, Zhuang G, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci U S A, 2011, 108(28):11590-11595.
26.	罗金龙, 姜淮芜. 胎盘生长因子与肿瘤的研究进展. 中国普外基础与临床杂志, 2014, 21(8):1046-1050.

1. 陈静, 张德巍, 张春东, 等. 术前血清CEA、CA19-9水平检测对胃癌术后复发转移及预后的意义. 中国普外基础与临床杂志, 2015, 22(2):195-199.
2. Rasmussen JG, Riis SE, Frøbert O, et al. Activation of protease-activated receptor 2 induces VEGF independently of HIF-1. PLoS One, 2012, 7(9):e46087.
3. 石岩岩, 丁士刚. 胃癌病因及发病机制的研究进展. 中华临床医师杂志:电子版, 2013, 7(17):7941-7944.
4. Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res, 2002, 62(10):2749-2752.
5. Chang LH, Pan SL, Lai CY, et al. Activated PAR-2 regulates panc-reatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis. Am J Pathol, 2013, 183(2):566-575.
6. 张示杰, 吴何兴, 李琪, 等. 沙鼠肝泡球蚴组织中微血管密度、血管内皮生长因子的表达及意义. 中国普外基础与临床杂志, 2015, 22(2):134-138.
7. Parr C, Watkins G, Boulton M, et al. Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur J Cancer, 2005, 41(18):2819-2827.
8. Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell cancer:an association with clinical characteristics and vascular endothelial growth factor levels. Anticancer Res, 2003, 23(6D):4953-4958.
9. Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in lung cancer. Tumor Biol, 2004, 25(1-2):1-6.
10. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma-2nd English edition. Gastric Cancer, 1998, 1(1):10-24.
11. 罗旭. PLGF、TGF β1和bFGF在膀胱移行细胞癌中的表达及临床意义. 遵义:遵义医学院, 2009:1-30.
12. 沈承澜, 沈振斌, 陈伟东. 血管内皮生长因子、缺氧诱导因子-1α在胃癌中的表达及其对预后影响的研究. 中国全科医学, 2010, 13(22):2460-2463.
13. De Falco S. The discovery of placenta growth factor and its biolo-gical activity. Exp Mol Med, 2012, 44(1):1-9.
14. Boyaud F, Inguimbert N. Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475). Expert Opin Ther Pat, 2011, 21(6):971-975.
15. Xu L, Cochran DM, Tong RT, et al. Placenta growth factor overex-pression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res, 2006, 66(8):3971-3977.
16. 张力建, 陈晋峰, 陆爱萍, 等. 胎盘生长因子和色素上皮衍生因子在非小细胞肺癌中的表达及其与预后的关系. 中华医学杂志, 2005, 85(47):3328-3331.
17. Waldner MJ, Neurath MF. Colitis-associated cancer:the role of T cells in tumor development. Semin Immunopathol, 2009, 31(2):249-256.
18. Fitzpatrick TE, Lash GE, Yanaihara A, et al. Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor. Exp Cell Res, 2003, 283(2):247-255.
19. Lenderink T, Heeschen C, Fichtlscherer S, et al. Elevated placental growth factor levels are associated with adverse outcomes at four-year follow-up in patients with acute coronary syndromes. J Am Coll Cardiol, 2006, 47(2):307-311.
20. Takahashi A, Sasaki H, Kim SJ, et al. Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. Biochem Biophys Res Commun, 1999, 257(3):855-859.
21. Ho MC, Chen CN, Lee H, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett, 2007, 250(2):237-249.
22. Hamady ZZ, Cameron IC, Wyatt J, et al. Resection margin in patients undergoing hepatectomy for colorectal liver metastasis:a critical appraisal of the 1 cm rule. Eur J Surg Oncol, 2006, 32(5):557-563.
23. Kodama J, Seki N, Tokumo K, et al. Placenta growth factor is abundantly expressed in human cervical squamous cell carcinoma. Eur J Gynaecol Oncol, 1997, 18(6):508-510.
24. Sands M, Howell K, Costello CM, et al. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res, 2011, 12:17.
25. Yao J, Wu X, Zhuang G, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci U S A, 2011, 108(28):11590-11595.
26. 罗金龙, 姜淮芜. 胎盘生长因子与肿瘤的研究进展. 中国普外基础与临床杂志, 2014, 21(8):1046-1050.

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Expression and Clinical Significance of Placental Growth Factor in Gastric Cancer Tissue

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